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Biometric traits are unique characteristics of an individual's body or behavior that can be used for identification and authentication. Biometric authentication uses unique physiological and behavioral traits for secure identity verification. Traditional unimodal biometric authentication systems often suffer from spoofing attacks, sensor noise, forgery, and environmental dependencies. To overcome these limitations, our work presents multimodal biometric authentication integrated with the characteristics of electroencephalograph (EEG) signals and handwritten signatures to enhance security, efficiency, and robustness. EEG-based authentication uses the brainwave patterns' intrinsic and unforgeable nature, while signature recognition demonstrates an additional behavioral trait for effectiveness. Our system processes EEG data of an individual with 14-channel readings, and the signature with the images ensures a seamless fusion of both modalities.Combining physiological and behavioral biometrics, our approach will significantly decrease the risk of unimodal authentication, including forgery, spoofing, and sensor failures. Our system, evaluated on a dataset of 30 subjects with genuine and forged data, demonstrates a 97% accuracy. Designed for small organizations, the modular structure, low computation algorithms, and simplicity of the hardware promote deployment scalability.

Background: To evaluate the incidence and potential predisposing factors for the development of acute kidney injury (AKI) in asphyxiated neonates undergoing hypothermic treatment.

Methods: This retrospective study was conducted at the Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy. All neonates above 34 weeks of gestation diagnosed with hypoxic-ischemic encephalopathy (HIE) and treated with hypothermia, weighing more than 1800 g, admitted from January 1, 2013 to December 31, 2022, were included. AKI was defined according to the neonatal KDIGO classification.

Results: A total of 75 neonates were enrolled, including 13 (17%) with severe HIE. The incidence of AKI was 35%, with 62% of cases identified as a reduction in diuresis, 27% as changes in creatinine and oliguria, and only 11% as isolated creatinine elevation. The rate of AKI was significantly higher in infants with severe HIE (p < 0.001). The development of AKI added significantly (aOR = 41.2, p = 0.007) to the probability of death, even after adjusting for severe HIE. Infants who developed AKI required more inotropes, had higher rates of hyponatremia (serum sodium < 125 mEq/L), and were less likely to normalize lactate levels within 24 h of birth.

Conclusions: In asphyxiated newborns, reduced kidney perfusion can cause kidney impairment in nearly 40% of those undergoing treatment. Enhancing the detection of AKI is crucial for improving patient outcomes. We recommend proactive monitoring of lactate trends, urinary output, and serum sodium levels to enable early interventions that protect kidney function and improve outcomes for these vulnerable infants.

Background: Urinary extravasation (UE) in patients with posterior urethral valves (PUV), in the form of urinomas or urinary ascites, is thought to represent a pop-off mechanism. Previous literature has proposed a kidney protective mechanism, although this remains controversial. Here, we performed a matched comparison to assess the effect of UE on kidney outcomes.

Methods: We retrospectively reviewed our PUV database, including all patients diagnosed < 3 months of age with at least 1-year follow-up. We collected demographics, management, vesicoureteral reflux (VUR) status, and kidney function parameters. UE was defined as postnatal urinoma or urinary ascites. We performed both unadjusted and propensity-matched comparisons of patients with and without UE. Matching was used to balance age, diversion status, urinary tract infection history, presence of VUR, and nadir creatinine. The primary outcomes were 1-, 3-, and 5-year kidney outcomes.

Results: Of the 138 patients meeting inclusion criteria, 27 (20%) had UE (23 urinoma, 4 urinary ascites). The median age at presentation was 5 days. Six patients (26%) required percutaneous drainage, and the median time to resolution was 21 days. Patients with UE had significantly higher initial creatinine levels but no difference in nadir values. Of those with available data, 18 (18%) and 10 (14%) had chronic kidney disease (CKD) at 3 and 5 years. Overall, there was no difference in 3- and 5-year rates of CKD between patients with and without a history of UE.

Conclusions: In a matched comparison, UE was not associated with long-term adverse or beneficial effects on kidney function. This study provides further evidence that the presence of UE may not be a relevant prognostic factor in children with PUV.

Background: Pediatric chronic kidney disease (CKD) causes significantly impaired health-related quality of life (hrQOL) and caregiver burden, but no studies focus specifically on autosomal recessive polycystic kidney disease (ARPKD).

Methods: This prospective case-control study assessed hrQOL (using PedsQL®ESRD) and screened for psychosocial problems (strength and difficulties questionnaire (SDQ)) in 43 children with ARPKD. Fifty-eight caregivers reported on the disease's impact on family (FaBel) and their own QOL (Ulm inventory of parental caregiver QOL (ULQIE)). As controls, we questioned 36 matched healthy children and 57 parents under similar pandemic restrictions and used published historical controls (healthy and with advanced CKD).

Results: Patients were aged 9.0 ± 4.8 years with CKD stage G1-4 (45%), on dialysis (14%) or after kidney transplantation (26%). Nine patients had developmental delay secondary to medical complications. PedsQL®ESRD total scores correlated significantly to kidney function, but could not capture liver-specific symptoms. All 4 measures showed significant differences between treatment modalities with best scores in patients during CKD stages G1-4 and worst on dialysis, except SDQ, which was worst after transplantation. The most significant extra-renal risk factor for all 4 scores was developmental delay of the child. SDQ scores were elevated in contemporary vs. historical controls, but even further in ARPKD especially for peer relationship problems.

Conclusion: In summary, ARPKD causes significantly impaired hrQOL, psychosocial problems and caregiver burden, which were equal to, if not greater than, that of controls with more advanced kidney failure. Treatment modality and developmental delay were the most important risk factors.

Trial registration: Trial registered 06/2020 DRKS S00021059.

Chimeric antigen receptor (CAR)-modified T cells have garnered substantial attention due to their clinical success, culminating in six Food and Drug Administration-approved therapies for hematological malignancies. Notably, CD19-specific CAR T cell therapies have achieved remarkable clinical efficacy in treating B-cell malignancies, but these profound and durable responses are not observed in CAR T therapies targeting other indications, particularly solid tumors. Key design elements of CAR constructs - namely, antigen binding affinity and spacer length - play critical roles in determining T cell effector function and overall therapeutic effectiveness. Refining CAR designs may enhance T cell functionality, extend clinical application, and potentially apply CAR T cell therapies across a wider array of malignancies. In this study, affinity variant and spacer variant CARs targeting BCMA and DLL3 tumor antigens were evaluated using in vitro measurements of antigen-binding properties and effector function. Each panel of CARs spanned 2-3 logs of antigen binding affinity (BCMA: 181 pM KD to 74 nM KD, DLL3: 417 pM to 407 nM). Additionally, CAR T cells were challenged with tumor spheroids composed of BCMA⁺ H929 and DLL3⁺ SHP77 tumor cells. We show that for both tumor models, higher affinity CARs (KD stronger than approximately 100 nM) paired with an intermediate length spacer (IgG1 Fc, CH2-CH3, 230AA) elicited the strongest levels of tumor killing, CAR⁺ T cell expansion, and proinflammatory cytokine production. These CARs displayed the strongest cellular affinity when measured in a conjugation assay, suggesting a relationship between cellular affinity and T cell functional performance. This study highlights the critical role of CAR design in enhancing T cell functionality, demonstrating that high-affinity CARs combined with intermediate-length spacers yield superior performance in targeting BCMA and DLL3 antigens. This study provides a framework for rational CAR design, informing strategies to broaden the clinical utility of CAR T-cell therapies beyond hematologic cancers.

T-cell receptor mimic (TCRm) antibodies are an emerging class of tumor-targeting agents used in advanced immunotherapies such as bispecific T-cell engagers and CAR-T cells. Unlike conventional antibodies, TCRms are designed to recognize peptide - human leukocyte antigen (pHLA) complexes that present intracellular tumor-derived peptides on the cell surface. Due to the typically low surface abundance and high sequence similarity of pHLAs, TCRms require high affinity and exceptional specificity to avoid off-target toxicity. Conventional methods for off-target identification such as sequence similarity searches, motif-based screening, and structural modeling focus on the peptide and are limited in detecting cross-reactive peptides with little or no sequence homology to the target. To address this gap, we developed EpiPredict, a TCRm-specific machine learning framework trained on high-throughput kinetic off-target screening data. EpiPredict learns an antibody-specific mapping from peptide sequence to binding strength, enabling prediction of interactions with unmeasured pHLA sequences, including sequence-dissimilar peptides. We applied EpiPredict to two distinct TCRms targeting the cancer-testis antigen MAGE-A4. The model successfully predicted multiple off-targets with minimal sequence similarity to the intended epitope, many of which were experimentally validated via T2 cell binding assays. These findings establish EpiPredict as a valuable tool for lead optimization of TCRms, enabling the identification of antibody-specific off-targets beyond the scope of traditional peptide-centric methods and supporting the preclinical de-risking of TCRm-based therapies.

Context: Several coumarins have been isolated from Ruta graveolens L., but the chirality of many remains uncharacterized or their absolute configurations unresolved.

Objective: This study aimed to comprehensively separate and characterize the chirality of 3'-methyl-3'-butenylcoumarins from R. graveolens extracts, determine their absolute configurations, and evaluate their anticoagulant and anti-inflammatory activities.

Materials and methods: Comprehensive chromatographic separation and chiral HPLC analysis were employed on the R. graveolens extract. The structures of isolated compounds were elucidated using extensive spectroscopic data analysis (HR-ESI-MS, NMR) and by comparing experimental circular dichroism (CD) spectra with calculated electronic circular dichroism (ECD) spectra. The anticoagulant and anti-inflammatory (specifically inhibition of nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages) activities of the isolated compounds were evaluated.

Results: The study led to the isolation of two pairs of enantiomeric 3'-methyl-3'-butenylcoumarins, present in both equivalent and inequivalent ratios. This included two previously undescribed chiral 3'-methyl-3'-butenylcoumarins with specific absolute configurations [(+)-2'R-2 and (-)-2'S-3] and one undescribed achiral 3'-methyl-3'-butenylcoumarin (1). Among the tested compounds, only the racemic mixture (±)-3 exhibited moderate inhibition of NO production in the anti-inflammatory assay. No significant anticoagulant activity was reported for the compounds.

Conclusions: This study successfully characterized the chirality and determined the absolute configurations of specific 3'-methyl-3'-butenylcoumarins from R. graveolens, including the discovery of three new compounds. While most isolated compounds lacked significant anticoagulant or anti-inflammatory activity in the tested models, racemic (±)-3 showed moderate anti-inflammatory potential by inhibiting NO production. These findings provide new insights for the future development and utilization of coumarins from R. graveolens.

Background: Integrating electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) with naturalistic stimuli has advanced our understanding of the neural mechanisms underlying mental disorders. Naturalistic paradigms use dynamic, multimodal stimuli that capture complex emotional and cognitive processes more effectively than traditional experimental designs. Objective: This review synthesizes research from 2014 to 2024 exploring neural mechanisms of anxiety, depression, and schizophrenia within naturalistic paradigms. Methods: Recent EEG-fMRI studies employing naturalistic tasks were examined to identify common and disorder-specific neural alterations across affective and cognitive networks. Results: In anxiety, hyperactivity in the amygdala, prefrontal cortex, anterior cingulate cortex, and insula, together with changes in the dorsal attention, default mode, and frontoparietal networks, reflects excessive fear responses and impaired regulation. Depression is characterized by disruptions in default mode and frontoparietal connectivity and altered amygdala-prefrontal interactions, indicating maladaptive introspection and cognitive control. Schizophrenia shows abnormalities in motor and language processing, with aberrant activity in frontal, parietal, and temporal regions including the insula and temporoparietal junction. Conclusion: These findings highlight the shared involvement of the amygdala, prefrontal cortex, anterior cingulate cortex, and insula across disorders and demonstrate the potential of naturalistic paradigms for advancing personalized diagnostics and interventions in mental health.